Author, as appears in the article.: Ceperuelo-Mallafre, Victoria; Reverte, Laia; Peraire, Joaquim; Madeira, Ana; Maymo-Masip, Elsa; Lopez-Dupla, Miguel; Gutierrez-Valencia, Alicia; Ruiz-Mateos, Ezequiel; Buzon, Maria Jose; Jorba, Rosa; Vendrell, Joan; Auguet, Teresa; Olona, Montserrat; Vidal, Francesc; Rull, Anna; Fernandez-Veledo, Sonia
Department: Medicina i Cirurgia Bioquímica i Biotecnologia
URV's Author/s: Auguet Quintillà, Maria Teresa / Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Jorba Martin, Rosa Maria / López Dupla, Jesús Miguel / Maymo Masip, Elsa / Olona Cabases, Maria Montserrat / Peraire Forner, José Joaquin / RULL AIXA, ANNA / Vendrell Ortega, Juan José / Vidal Marsal, Francisco
Keywords: Tricarboxylic acids Succinates Succinate Semi-targeted metebolomics Sars-cov-2 Pyruvic acid Pyruvate Prognosis Lactates Ketoglutaric acids Humans Glucose Fluorometric quantification Energy-related metabolites Creatinine Covid-19 C-reactive protein Biomarkers
Abstract: BackgroundCoronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. MethodsWe used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and alpha-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. ResultsIncreased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 mu M; p<0.001) as an early criterion to accurately classify patients with critical outcomes. ConclusionOur findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.
Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Immunology and allergy Immunology Farmacia Engenharias iii Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Biodiversidade
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: elsa.maymo@urv.cat joaquim.peraire@urv.cat victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat jvortega@iispv.cat mariateresa.auguet@urv.cat rosamaria.jorba@urv.cat francesc.vidal@urv.cat jesusmiguel.lopez@urv.cat
Author identifier: 0000-0002-9133-3120 0000-0001-7808-5479 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115 https://orcid.org/0000-0003-0396-6428 0000-0003-0396-6428 0000-0003-3307-4340 0000-0002-6692-6186 0000-0002-9141-2523
Record's date: 2024-12-21
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Frontiers In Immunology. 13 (912579): 912579-
APA: Ceperuelo-Mallafre, Victoria; Reverte, Laia; Peraire, Joaquim; Madeira, Ana; Maymo-Masip, Elsa; Lopez-Dupla, Miguel; Gutierrez-Valencia, Alicia; Ruiz- (2022). Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes. Frontiers In Immunology, 13(912579), 912579-. DOI: 10.3389/fimmu.2022.912579
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV